Articles: regulatory-t-lymphocytes.
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Am. J. Respir. Cell Mol. Biol. · Oct 2010
Programmed Death-1 antibody blocks therapeutic effects of T-regulatory cells in cockroach antigen-induced allergic asthma.
We recently reported that the adoptive transfer of T-regulatory cells (Tregs) isolated from lung and spleen tissue of green fluorescent protein-transgenic mice reversed airway hyperresponsiveness and airway inflammation. Because Programmed Death-1 (PD-1) is a pivotal receptor regulating effector T-cell activation by Tregs, we evaluated whether PD-1 is involved in the therapeutic effect of naturally occurring Tregs (NTregs) and inducible Tregs (iTregs) in cockroach (CRA)-sensitized and challenged mice. The CD4(+)CD25(+) NTregs and CD4(+)CD25(-) iTregs isolated from the lungs and spleens of BALB/c mice were adoptively transferred into CRA-sensitized and CRA-challenged mice with and without anti-PD-1 antibody (100 μg/mice). ⋯ These mice had substantially higher concentrations of BALF IL-4, IL-5, and IL-13, but significantly decreased levels of BALF IL-10. Adoptive therapy recipients without the anti-PD-1 antibody exhibited high levels of CTLA-4 expression and Foxp3 transcripts in lung CD4(+)CD25(+) T cells, with a significant decrease in BALF IL-4, IL-5, and IL-13 concentrations and a substantial increase in BALF IL-10 concentrations. These data suggest that the reversal of airway hyperresponsiveness and airway inflammation by Tregs is mediated in part by PD-1, because other costimulatory molecules (e.g., inducible costimulatory molecule [ICOS] or CTLA-4) have been shown to play a role in Treg-mediated suppression.
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T regulatory cells (Tregs) may play a role in the suppression of effector lymphocyte activity in asthma. We hypothesized that Treg numbers would be increased in patients with more severe asthma. We also investigated the regulatory function of CD4 cells by expression of cytotoxic T-lymphocyte antigen 4 (CTLA4), and the number of these cells that are intraepithelial lymphocytes expressing CD103. ⋯ The number of cells displaying regulatory capacity, either through FoxP3 expression or CTLA4 expression, is increased in moderate to severe asthma. CD4(+)CD103(+) intraepithelial lymphocytes can be retained at tissue sites of inflammation; our findings indicate a role for these cells in asthma pathophysiology.
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Clin. Exp. Immunol. · Sep 2010
Indication for a role of regulatory T cells for the advent of influenza A (H1N1)-related pneumonia.
Regulatory T cells (T(regs) ) have an anti-inflammatory role. A former study in a limited number of patients found that absolute counts of T(regs) increase when infection by the new influenza H1N1 virus is complicated with pneumonia. These results generate the question if H1N1-related pneumonia is associated with a state of hypo-inflammation. ⋯ Regression analysis revealed that the most important factors related with the advent of pneumonia were the existence of underlying illnesses (P = 0·006) and of T(regs) equal to or above 16 mm(3) (P = 0·013). It is concluded that the advent of H1N1-related pneumonia is related to an early increase of the absolute T(reg) counts. This increase is probably not part of a hypo-inflammatory state of the host.
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High-dose interferon-alpha 2b (IFN-alpha 2b) is the only approved systemic therapy in the United States for the adjuvant treatment of melanoma. The study objective was to explore the immunomodulatory mechanism of action for IFN-alpha 2b by measuring serum regulatory T cell (Treg), serum transforming growth factor-beta (TGF-beta), interleukin (IL)-10, and autoantibody levels in patients with melanoma treated with the induction phase of the high-dose IFN-alpha 2b regimen. ⋯ Patients with melanoma in this study showed increased basal levels of Treg that may be relevant to their disease and its progression. Treg levels shifted in patients with melanoma treated with IFN-alpha 2b, although no firm conclusions regarding the role of Tregs as a marker of treatment response or outcome can be made at present.
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Critical care medicine · Aug 2010
Comparative StudyRole of regulatory T cells in long-term immune dysfunction associated with severe sepsis.
To investigate the role of regulatory T cells in the modulation of long-term immune dysfunction during experimental sepsis. It is well established that sepsis predisposes to development of a pronounced immunosuppression. Nevertheless, the mechanisms underlying the immune dysfunction after sepsis are still not well understood. ⋯ These findings suggest that regulatory T cells play an important role in the progression and establishment of immune dysfunction observed in experimental sepsis.